IGHG1⁺ plasma cells define an NF-κB-driven inflammatory program that shapes T-cell immunity and immunotherapy response in colorectal cancer

作者：Zhang RF, Zhang WZ, Li H, Chen Y, Zhong R, Wang JF · 发表于：Translational oncology · 年份：2026 · DOI：10.1016/j.tranon.2026.102930 · 被引用次数：38

BACKGROUND: The efficacy of immune checkpoint blockade (ICB) in colorectal cancer (CRC) is constrained by marked heterogeneity in the tumor microenvironment (TME). Although B cells and tertiary lymphoid structures (TLS) have emerged as important determinants of anti-tumor immunity, the functional diversity of plasma-cell subsets in CRC immunotherapy remains insufficiently understood. METHODS: We performed an integrative analysis combining public single-cell RNA sequencing data, validation in independent bulk transcriptomic immunotherapy cohorts, and in vitro and in vivo functional experiments. Tumor-infiltrating B-cell subsets were characterized at single-cell resolution, and an IGHG1⁺ plasma-cell-associated signature was constructed for external validation. RESULTS: We identified an IGHG1⁺ plasma-cell subset that was preferentially enriched in tumors from patients with favorable immunotherapy response. Within this compartment, High-IGHG1 plasma cells displayed a transcriptional program associated with antigen presentation, inflammatory signaling, and NF-κB pathway activation. Tumors enriched for this population showed coordinated expansion of activated T-cell states, particularly cytotoxic CD8+ subsets. An IGHG1⁺ plasma-cell signature derived from these findings predicted immunotherapy response across multiple independent cohorts and was associated with prolonged progression-free survival in external datasets. In transcriptome bulk CRC cohorts, the signature correlated wit...